Established in 1992, the Yale Older Americans Independence Center (OAIC) seeks to continue providing intellectual leadership and innovation for aging research that aims to enhance independence. Our unifying theme remains the investigation of multifactorial geriatric health conditions, encompassing single conditions resulting from multiple contributing factors or affecting multiple outcome domains and multiple conditions occurring simultaneously. Our premise is that health conditions common in older adults are determined by the co-occurrence of multiple predisposing and precipitating factors. These conditions and factors, in turn, affect a range of health domains. The predisposing factors may be at genetic, physiologic (impairment), disease, or socio-demographic levels, while the precipitating factors may be behavioral, environmental, social, medical, or psychological. What distinguishes Yale OAIC research is that its purpose is to investigate the interactions among, or intervene on, multiple factors simultaneously and to measure the effect of conditions or interventions on a range of health domains. The Aims of the Yale OAIC are to: 1) develop the careers of future academic leaders in aging/geriatrics;2) train investigators and methodologists in the skills necessary to design, conduct, and analyze studies of multifactorial geriatric health conditions; 3) develop design and analytic techniques for conducting studies of multifactorial geriatric health conditions; 4) develop strategies for recruiting into, and retaining, a broad spectrum of older adults, including minorities, into OAIC studies; 5) investigate the causative mechanisms of, and identify effective treatments for, health conditions experienced by older adults from a multifactorial research perspective; 6) develop outcome measures for use in investigating multifactorial geriatric health conditions and for studying older adults with multiple coexisting conditions; and 7) facilitate basic, translational, and interdisciplinary research that connects to our focus on multifactorial geriatric health conditions. The Yale OAIC cores include: 1) Leadership / Administrative; 2) Research Career Development; 3) Pilot/Exploratory; 5) Biostatistics; 6) Data Management / Informatics; and 7) Field. For the first years of the next cycle, we propose to support 4 RCDC candidates; 4 pilot studies (including 2 by RCDC candidates); 1 computational biology development study; and 14 externally funded projects.